ID   TWMD_TALWO              Reviewed;         512 AA.
AC   A0A2L0P0J8;
DT   07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT   25-APR-2018, sequence version 1.
DT   03-AUG-2022, entry version 12.
DE   RecName: Full=Cytochrome P450 monooxygenase TwmD {ECO:0000303|PubMed:29343058};
DE            EC=1.-.-.- {ECO:0000305|PubMed:29343058};
DE   AltName: Full=Wortmanamides biosynthesis cluster protein D {ECO:0000303|PubMed:29343058};
GN   Name=TwmD {ECO:0000303|PubMed:29343058};
GN   Synonyms=TwnD {ECO:0000303|PubMed:29343058};
OS   Talaromyces wortmannii (Penicillium wortmannii).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Trichocomaceae; Talaromyces;
OC   Talaromyces sect. Islandici.
OX   NCBI_TaxID=28567;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC   STRAIN=ATCC 26942 / CBS 387.67 / CCM F-175 / VKM F-2091;
RX   PubMed=29343058; DOI=10.1021/jacs.7b13350;
RA   Hai Y., Tang Y.;
RT   "Biosynthesis of long-chain N-acyl amide by a truncated polyketide
RT   synthase-nonribosomal peptide synthetase hybrid megasynthase in fungi.";
RL   J. Am. Chem. Soc. 140:1271-1274(2018).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of wortmanamides A and B, reduced long-chain
CC       polyketides amidated with a specific omega-amino acid, 5-aminopentanoic
CC       acid (5PA) (PubMed:29343058). The PKS modules of TwmB are involved in
CC       the synthesis of the polyketide backbone, whereas the non-canonical C
CC       domain of TwmB is a bonafide condensation domain that specifically
CC       selects 5PA and catalyzes amidation to release polyketide chain
CC       (PubMed:29343058). The C domain clearly prefers C16 and C18 fatty acyl
CC       substrates, which is consistent with simultaneous formation of both
CC       octaketide and nonaketide acyl amides wortmanamides A and B
CC       (PubMed:29343058). Because TwmB lacks a designated enoylreductase (ER)
CC       domain, the required activity is provided the enoyl reductase TwmE
CC       (PubMed:29343058). The roles of the remaining enzymes have still to be
CC       clarified (Probable). {ECO:0000269|PubMed:29343058,
CC       ECO:0000305|PubMed:29343058}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:29343058}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; MG837521; AUY61972.1; -; Genomic_DNA.
DR   EMBL; MH399766; QBC19712.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A2L0P0J8; -.
DR   SMR; A0A2L0P0J8; -.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002401; Cyt_P450_E_grp-I.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   SUPFAM; SSF48264; SSF48264; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   3: Inferred from homology;
KW   Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase.
FT   CHAIN           1..512
FT                   /note="Cytochrome P450 monooxygenase TwmD"
FT                   /id="PRO_0000452490"
FT   BINDING         454
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:P04798"
SQ   SEQUENCE   512 AA;  58750 MW;  25C8BD64477A6ACF CRC64;
     MAFLDYPPFD ICTIQQLLTF IIISYTFYLT TRSIWRLYFH PLSKYPGPKV AAISDIWYAY
     HALAGRWPWA VADALEKYGD VVRIAPNEIA FVTPKALSDI YGSHNKNLEN FAKTQINNHG
     NDEHGGLIWE WDPARHREVA RQLSPAFSGR ALRAKEATLH KYIDLFVERM TTLGGETGGV
     SLPTWINWLC VDISADMAYN REMNALKDMK EPPYLSILSG FNRAVVVTQM SWRFPLLSPL
     KGLFLAITAM RSHSHIRNHS RFQLEQRIRR KGAVEHLDFF EQLIPENREP PKDRKEMRHL
     EQVAGQLLVA GYEPPALWFY FTIYYLLKNP ATLDTLTKEI RSAFKNYDEI TSGSAAQLAY
     LSACLSESLR IMPGVLTGMP VVSPGAMVDG TYIPKGVVCQ SSSLALARSP RNFRHALSFR
     PERWLQEDHA LYDAQFAQDN RKGFQPFSQG PRICAGKEIA WWQSRVFLAK VLWTFDLEMV
     SGQQIDMARD LRGWGMYDKP EIRVRFRPKF VV